Effects of Flavonoides from the Leaves of Acanthopanax on the Activity of CYP450 Isozymes in Rat Liver Microsomes by a UPLC-MS/MS and Cocktail Probe Substrates Method

Effects of flavonoides including quercitrin, hyperoside and rutin from the leaves of Acanthopanax on the activity of hepatic microsomal CYP450 isozymes(CYP1A2, CYP2C, CYP2E1, CYP2D and CYP3A) in rat liver microsomes were analyzed by a ultra performance liquid chromatography-tandem mass spectrometry (multiple reaction monitoring) [UPLC-MS/MS(MRM)] combined with cocktail probe substrates method. The results showed that three compounds on the activities of some CYP450 isozymes were the inhibitory effects using rat liver microsomes, in which the IC50 values of quercitrin and hyperoside to the inhibition of rat microsomal CYP1A2 activity were 46. 53 and 49. 75 mu mol/L, respectively, the IC50 values of hyperoside and rutin for the inhibition of CYP2E1 activity were 99. 87 and 86. 36 mu mol/L, respectively. Mechanism of inhibition experimental results show that three compounds on each CYP450 isozymes inhibiting ability was increased with the increasing of the preincubation time, therefore, the inhibitory effects was a mechanism-based inhibition.